REGN-COV2 antibody cocktail may reduces viral load in Covid-19 patients

1. In this interim analysis, patients who received REGN-COV2 had significantly greater decreases in viral load from baseline compared to those who received placebo.

2. Those who received REGN-COV2 were also only only half as likely to require additional medically attended visits compared to those in the placebo group.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Most people who are infected with SARS-CoV-2 are either asymptomatic or can be treated on an outpatient basis, but a smaller subset develops hypoxemia and requires supplemental oxygen or hospitalization. These patients typically have high viral titers, leading many to hypothesize that reducing viral load may lead to a lesser likelihood of severe Covid-19. REGN-COV2 is a cocktail composed of equal amounts of two noncompeting, neutralizing human IgG1 antibodies (casirivimab and imdevimab) that both target the receptor-binding domain of the SARS-CoV-2 spike protein. In nonhuman primates, this formula has been shown to dramatically reduce viral replication when administered prophylactically and accelerate viral clearance when administered therapeutically. In the phase 1-2 portion of this ongoing trial involving adults with mild Covid-19, it was discovered that those who received REGN-COV2 had a significantly greater decrease in viral load compared to those who received placebo. This effect was rapid, with most reduction occurring within 2 days, and it was most pronounced in patients who were antibody-negative at baseline, which suggests that this treatment may be most effective in those whose endogenous immune systems have yet to be activated. Patients who received REGN-COV2 also had fewer medically attended visits related to Covid-19 compared to those in the placebo group. Serious adverse events were infrequent in both groups, and pharmacokinetics were linear and dose-proportional with no evidence of the development of antidrug antibodies. Of note, the half-life of the antibodies was longer than expected, suggesting that REGN-COV2 treatment may confer some degree of long-term passive immune.

Click here to read the study in NEJM

Relevant Reading: REGN-COV2 antibodies prevent and treat SARS-CoV-2 infection in rhesus macaques and hamsters

In-Depth [randomized controlled trial]: In the phase 1-2 portion of this ongoing trial, 269 adult patients were randomly assigned in a 1:1:1 ratio to receive high dose REGN-COV2 (8.0 g), low-dose REGN-COV2 (2.4 g), or placebo intravenously. At baseline, 123 patients (45%) were serum antibody-positive, 113 (41%) were serum antibody-negative, and 39 (14%) had unknown antibody status. The serum antibody-positive patients and serum antibody-negative patients had median viral loads of 3.49 log₁₀ copies per milliliter and 7.18 log₁₀ copies per milliliter, respectively. Patients were followed through day 7 for changes in viral load and through day 29 for the frequency of Covid-19–related medically attended visits. Patients who received REGN-COV2 had greater reductions in viral load compared to placebo, with the least-squares mean differences from placebo being−0.25 log₁₀ copies per milliliter (95% CI, −0.60 to 0.10) for the low-dose group, −0.56 log₁₀ copies per milliliter (95% CI, −0.91 to −0.21) for the high-dose group, and −0.41 log₁₀ copies per milliliter (95% CI, −0.71 to −0.10) for the combined group. This effect was driven primarily by patients who were serum antibody-negative at baseline; for this subgroup, the least-squares mean difference from placebo were −0.52 log₁₀ copies per milliliter (95% confidence interval [CI], −1.04 to 0.00), −0.60 log₁₀copies per milliliter (95% CI, −1.12 to −0.08), and −0.56 log₁₀ copies per milliliter (95% CI, −1.02 to −0.11), respectively. Similarly, 6 of 182 patients (3%) in the combined REGN-COV2 group and 6 of 93 patients (6%) in the placebo group had a medically attended visit (relative difference, −49 percentage points; absolute difference, −3 percentage points; 95% CI, −16 to 9). Again, this effect was magnified in the the serum antibody-negative subgroup; 5 of 80 patients (6%) in the combined REGN-COV2 group had a medically attended visit compared to 5 of 33 patients (15%) in the placebo group (relative difference, −59 percentage points, absolute difference, −9 percentage points; 95% CI, −29 to 11).

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